Steroid Therapy in Autoimmune Premature Ovarian Failure

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

ClinicalTrials.gov Identifier:

NCT00001306

First Posted: November 4, 1999

Last Update Posted: July 2, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

No therapy for infertile patients with premature ovarian failure has been proven effective. Some anecdotal reports have suggested that high dose, long term prednisone (steroid) therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-doses for long periods of time has substantial side effects, including aseptic necrosis of bone where portions of bone die without the presence of infection and are surrounded by healthy tissue. Aseptic necrosis of bone often requires major surgical treatment. Even with this known level of risk, patients with premature ovarian failure are being treated based on this anecdotal evidence.

This study will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will cause a remission of autoimmune ovarian failure. There is no reliable blood test to identify patients who have premature ovarian failure. Therefore, all patients must undergo a laparoscopic ovarian biopsy to confirm the presence of an auto immune reaction in the ovaries (autoimmune oophoritis). Laparoscopy is a surgical procedure that allows doctors to explore the abdomen using a camera-like device called a laparoscope. The procedure has been used clinically by some reproductive endocrinologists to identify patients with premature ovarian failure who have an autoimmune mechanism for the disorder.

The treatment will be deemed successful based on the return of ovulation as determined by weekly serum progesterone levels.

Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment:

33

Study Start Date:

July 10, 1992

Estimated Study Completion Date:

December 12, 2011

Detailed Description:

Autoimmune oophoritis is a distinct clinical entity and a known cause of premature ovarian failure. It is characterized by the presence of circulating adrenal antibodies. No therapy for infertile patients with premature ovarian failure due to autoimmune oophoritis has been proven effective by prospective controlled study. Anecdotal reports have suggested that high-dose, long-term prednisone therapy may be useful in treating autoimmune ovarian failure. However, prednisone, when used in high-dose for a long-term has substantial side effects, including aseptic necrosis of bone requiring major surgical intervention. Despite this risk, patients with premature ovarian failure are being treated based on this anecdotal evidence. We are aware of two patients with premature ovarian failure who developed aseptic necrosis of bone on high-dose, long-term prednisone therapy administered elsewhere.

This protocol will test the hypothesis that a lower risk therapy (alternate-day, lower dose, shorter-term prednisone) will induce remission of ovarian failure caused by autoimmune oophoritis. The protocol will use a double-masked, placebo-controlled design. Patients with premature ovarian failure who have serologic evidence of steroidogenic cell autoimmunity will be candidates. Successful outcome will be defined as a return of ovulation as determined by weekly serum progesterone levels. The hypothesis that short-term, alternate-day prednisone therapy restores ovulation will be tested with an equality of proportions test comparing the proportion of patients who ovulate during placebo with the proportion of patients who ovulate during prednisone therapy.

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:

18 Years to 39 Years (Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

INCLUSION/EXCLUSION CRITERIA:

Women 18 to 39 years of age with premature ovarian failure who meet the following requirements will be candidates for the study:

At least a four month history of amenorrhea not due to pregnancy,

Clearly elevated gonadotropins with a serum FSH greater than or equal to 40 IU/L on two separate occasions at least one month apart,

Positive adrenal or ovarian antibodies demonstrated by indirect immuno-fluorescence using monkey tissue as substrate or other laboratory evidence of steroidogenic cell autoimmunity such as the presence of antibodies against 21-hydroxylase,

No evidence for genetic, metabolic, toxic, or iatrogenic cause of the ovarian failure,

No medical contraindication to glycocorticoid therapy,

No glycocorticoid therapy taken in the past year (patients on appropriate replacement therapy for Addison's disease are not excluded),

No medical contraindication to pregnancy.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001306

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)